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We evaluated two scalable strategies to generate ARMMs loaded with protein cargo, by transient transfection or stable cell line-based production. The upstream ARMMs production processes utilized a suspension-adapted HEK293-derived line, termed 5B8. 5B8 cells yielded robust production of ARMMs after transient transfection with the ARMMs loading construct or using a stable cell line containing a transgene that encodes the ARMMs loading cassette, in shake flasks or a stirred tank bioreactor, respectively. ARMMs were purified by ultracentrifugation (small scale) or a combination of TFF and AEX (scalable production). Both purification methods produced comparable ARMMs, in terms of size and payload incorporation. Single particle analysis showed approximately 50% were payload-containing ARMMs. Additionally, an in vivo study was conducted in mice to investigate the half-life and biodistribution of ARMMs administered intravenously. ARMMs showed rapid biodistribution predominantly to the spleen and liver and, to a lesser extent, kidneys, and lungs. The half-life of ARMMs in plasma was 6\u2009\u00b1\u20090.4\u00a0min. Altogether, this work advances knowledge on scale-up of engineered cell-derived vesicles for future in vivo delivery of therapeutic molecules.<\/jats:p>","DOI":"10.1038\/s41598-025-87674-5","type":"journal-article","created":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T04:59:14Z","timestamp":1740805154000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Scalable production and purification of engineered ARRDC1-mediated microvesicles in a HEK293 suspension cell system"],"prefix":"10.1038","volume":"15","author":[{"given":"Kristin","family":"Luther","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Navaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Gens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carson","family":"Semple","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pearl","family":"Moharil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Passalacqua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Komal","family":"Vyas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Lin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senthil","family":"Ramaswamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Zocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F.","family":"Nabhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"key":"87674_CR1","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/s41419-022-05034-x","volume":"13","author":"M Kou","year":"2022","unstructured":"Kou, M. et al. 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